Primary biliary cirrhosis. High proportions of B cells in blood and liver tissue produce anti-mitochondrial antibodies of several Ig classes.

Anti-mitochondrial Abs (AMA) of the M2 type are recognized as being specific for primary biliary cirrhosis (PBC). We developed a highly specific assay to detect single AMA-producing cells using pyruvate dehydrogenase (PDH), the major Ag for AMA. Total Ab and AMA production of in vivo activated B cells was measured in peripheral blood from 13 PBC patients, 22 patients with other liver diseases, and 15 healthy controls. Anti-PDH-producing cells, PDH spot-forming cells (PDH-SFC), were detected in 12 of 13 PBC patients and represented a very high proportion of circulating Ig-producing lymphocytes (9 +/- 8.6%; mean +/- SD). The autoantibodies were mainly of IgG and IgM Ig classes. The number of PDH-SFC was positively correlated with the numbers of total Ig-SFC within each Ig class. An increased number of total IgM SFC in blood was found in PBC patients compared with controls, and IgM SFC correlated with the elevated serum levels of IgM typical for this disease. Among the lymphocytes extracted from PBC liver tissue (n = 5), we detected PDH-SFC of IgG (range 0 to 33% of total SFC), IgM (0 to 42%), and IgA types (1 to 30%). IgA PDH-SFC were found in five of five livers, but only in two of thirteen blood samples investigated. Taken together, our data reveal that very high numbers of B cells spontaneously produce disease-specific autoantibodies in blood and liver tissue in PBC. Furthermore, the Ig class distribution of produced autoantibody differs between these two compartments, and this may have pathogenetic significance.